Breathomics: may it become an affordable, new tool for early diagnosis of non-small-cell lung cancer? An exploratory study on a cohort of 60 patients.

OBJECTIVES: Analysis of breath, specifically the patterns of volatile organic compounds (VOCs), has shown the potential to distinguish between patients with lung cancer (LC) and healthy individuals (HC). However, the current technology relies on complex, expensive and low throughput analytical platforms, which provide an offline response, making it unsuitable for mass screening. A new portable device has been developed to enable fast and on-site LC diagnosis, and its reliability is being tested. METHODS: Breath samples were collected from patients with histologically proven non-small-cell lung cancer (NSCLC) and healthy controls using Tedlar bags and a Nafion filter attached to a one-way mouthpiece. These samples were then analysed using an automated micro portable gas chromatography device that was developed in-house. The device consisted of a thermal desorption tube, thermal injector, separation column, photoionization detector, as well as other accessories such as pumps, valves and a helium cartridge. The resulting chromatograms were analysed using both chemometrics and machine learning techniques. RESULTS: Thirty NSCLC patients and 30 HC entered the study. After a training set (20 NSCLC and 20 HC) and a testing set (10 NSCLC and 10 HC), an overall specificity of 83.3%, a sensitivity of 86.7% and an accuracy of 85.0% to identify NSCLC patients were found based on 3 VOCs. CONCLUSIONS: These results are a significant step towards creating a low-cost, user-friendly and accessible tool for rapid on-site LC screening. CLINICAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT06034730.

PARP inhibitor and immune checkpoint inhibitor have synergism efficacy in gallbladder cancer.

Gallbladder cancer (GBC) is an aggressive cancer with poor prognosis. PARP inhibitors (PARPi) target PARP enzymes and have shown efficacy in patients with breast cancer gene (BRCA) mutations. Immunotherapy, especially immune checkpoint inhibitors (ICIs), has transformed cancer treatment. However, the combined impact of PARPi and ICIs in GBC remains unclear. We present a groundbreaking case of a GBC patient with BRCA2 mutations who received combination therapy with PARPi and ICIs after failing multiple lines of treatment. Next-generation sequencing (NGS-Seq) identified BRCA gene mutations. To further investigate potential mechanisms, we developed a PARP1-BRCA1-BRCA2 pathway-related risk score (PBscore) system to evaluate the impact of PARPi on the tumor immune microenvironment via RNA-Seq data. Gene expression and functional analysis identified potential mechanisms associated with the PBscore. Experimental validation assessed the impact of the combination therapy on the tumor microenvironment using multiplexed immunofluorescence imaging and immunohistochemistry in patients with BRCA gene wild type or mutations. RNA-Seq analysis revealed correlations between PBscore, immune checkpoint levels, tumor-infiltrating immune cells (TIICs), and the cancer-immunity cycle. Multiplexed immunofluorescence imaging validated that low PBscore patients might have an active tumor microenvironment. Furthermore, upon drug resistance, we observed an upregulation of negative immune checkpoints such as CEACAM1, indicating that the tumor immune microenvironment becomes suppressed after resistance. Our study revealed that PBscore could serve as a biomarker to predict immunotherapy efficacy, offering a promising alternative for BRCA2-mutated GBC patients.

Identification of a novel waikavirus infecting Pittosporum tobira in China.

A novel waikavirus, tentatively named "Pittosporum tobira waikavirus" (PtWV), was identified in Pittosporum tobira plants exhibiting mosaic and ringspot symptoms on foliage in Yunnan, China. The full-length genomic sequence was determined by high-throughput sequencing and rapid amplification of cDNA ends. The genome of PtWV is 12,709 nt in length and has a large open reading frame (ORF) of 11,010 nt, encoding a polyprotein, and a small ORF that encodes a 13.2-kDa bellflower vein chlorosis virus (BVCV)-like protein. Phylogenetic analysis and sequence alignment revealed that PtWV is closely related to actinidia yellowing virus 1 (AcYV1), which shares the highest amino acid (aa) sequence similarity (50.1% identity) in the Pro-RdRp region. To the best of our knowledge, this is the first report of a novel waikavirus in P. tobira.

Colorectal Cancer Diagnosis through Breath Test Using a Portable Breath Analyzer-Preliminary Data.

Screening methods available for colorectal cancer (CRC) to date are burdened by poor reliability and low patient adherence and compliance. An altered pattern of volatile organic compounds (VOCs) in exhaled breath has been proposed as a non-invasive potential diagnostic tool for distinguishing CRC patients from healthy controls (HC). The aim of this study was to evaluate the reliability of an innovative portable device containing a micro-gas chromatograph in enabling rapid, on-site CRC diagnosis through analysis of patients' exhaled breath. In this prospective trial, breath samples were collected in a tertiary referral center of colorectal surgery, and analysis of the chromatograms was performed by the Biomedical Engineering Department. The breath of patients with CRC and HC was collected into Tedlar bags through a Nafion filter and mouthpiece with a one-way valve. The breath samples were analyzed by an automated portable gas chromatography device. Relevant volatile biomarkers and discriminant chromatographic peaks were identified through machine learning, linear discriminant analysis and principal component analysis. A total of 68 subjects, 36 patients affected by histologically proven CRC with no evidence of metastases and 32 HC with negative colonoscopies, were enrolled. After testing a training set (18 CRC and 18 HC) and a testing set (18 CRC and 14 HC), an overall specificity of 87.5%, sensitivity of 94.4% and accuracy of 91.2% in identifying CRC patients was found based on three VOCs. Breath biopsy may represent a promising non-invasive method of discriminating CRC patients from HC.

1D-Guided Differential Rescaling of a Contour Plot in Comprehensive 2D Gas Chromatography.

A 1D-guided differential rescaling algorithm for a contour plot is developed based on our recently proposed comprehensive two-dimensional gas chromatography (GC × GC) system with a first-dimensional (1D) detector added. Chromatograms obtained from 1D and second-dimensional (2D) detectors are both incorporated during the data processing. As compared to the conventional contour plot methods using only 2D data, our algorithm can significantly improve precision and consistency of GC × GC results in terms of retention times, peak widths, and peak areas or volumes, regardless of modulation time selection, modulation phase shift fluctuations, and modulation duty cycle. The peak identification, quantification, and capacity can therefore be enhanced. Furthermore, the 1D-guided differential rescaling method is shown to better handle the coelution and missing peak issues often encountered in the conventional methods. Finally, the new method exhibits high versatility in 1D and 2D detector selection, which greatly broadens GC × GC utility. Our method can easily be adapted to other two-dimensional chromatography systems that have direct access to 1D chromatograms.

Recent advances in bimetallic nanoscale zero-valent iron composite for water decontamination: Synthesis, modification and mechanisms.

The environmental pollution of water is one of the problems that have plagued human society. The bimetallic nanoscale zero-valent iron (BnZVI) technology has increased wide attention owing to its high performance for water treatment and soil remediation. In recent years, the BnZVI technology based on the development of nZVI has been further developed. The material chemistry, synthesis methods, and immobilization or surface stabilization of bimetals are discussed. Further, the data of BnZVI (Fe/Ni, Fe/Cu, Fe/Pd) articles that have been studied more frequently in the last decade are summarized in terms of the types of contaminants and the number of research literatures on the same contaminants. Five contaminants including trichloroethylene (TCE), Decabromodi-phenyl Ether (BDE209), chromium (Cr(VI)), nitrate and 2,4-dichlorophenol (2,4-DCP) were selected for in-depth discussion on their influencing factors and removal or degradation mechanisms. Herein, comprehensive views towards mechanisms of BnZVI applications including adsorption, hydrodehalogenation and reduction are provided. Particularly, some ambiguous concepts about formation of micro progenitor cell, production of hydrogen radicals (H·) and H2 and the electron transfer are highlighted. Besides, in-depth discussion of selectivity for N2 from nitrates and co-precipitation of chromium are emphasized. The difference of BnZVI is also discussed.

Automated Gas Chromatography Peak Alignment: A Deep Learning Approach using Greedy Optimization and Simulation.

The clinical significance of volatile organic compounds (VOC) in detecting diseases has been established over the past decades. Gas chromatography (GC) devices enable the measurement of these VOCs. Chromatographic peak alignment is one of the important yet challenging steps in analyzing chromatogram signals. Traditional semi-automated alignment algorithms require manual intervention by an operator which is slow, expensive and inconsistent. A pipeline is proposed to train a deep-learning model from artificial chromatograms simulated from a small, annotated dataset, and a postprocessing step based on greedy optimization to align the signals.Clinical Relevance- Breath VOCs have been shown to have a significant diagnostic power for various diseases including asthma, acute respiratory distress syndrome and COVID-19. Automatic analysis of chromatograms can lead to improvements in the diagnosis and management of such diseases.

Genomic characterization of a novel torradovirus infecting Arctium lappa L. in China.

Burdock (Arctium lappa L.) is not only a popular vegetable crop but also an important medicinal plant. In burdock plants with symptoms of leaf mosaic, a novel torradovirus tentatively named "burdock mosaic virus" (BdMV) was identified by high-throughput sequencing. The complete genomic sequence of BdMV was further determined using RT-PCR and the rapid amplification of cDNA ends (RACE) method. The genome is composed of two positive-sense single-stranded RNAs. RNA1 (6991 nt) encodes a polyprotein of 2186 aa, and RNA2 (4700 nt) encodes a protein of 201 aa and a polyprotein of 1212 aa that is predicted to be processed into one movement protein (MP) and three coat proteins (CPs). The Pro-Pol region of RNA1 and the CP region of RNA2 shared the highest amino acid sequence identity of 74.0% and 70.6%, respectively, with the corresponding sequences of lettuce necrotic leaf curl virus (LNLCV) isolate JG3. Phylogenetic analysis based on the amino acid sequences of the Pro-Pol and CP regions showed that BdMV clustered with other non-tomato-infecting torradoviruses. Taken together, these results suggest that BdMV is a new member of the genus Torradovirus.

Portable comprehensive two-dimensional micro-gas chromatography using an integrated flow-restricted pneumatic modulator.

Two-dimensional (2D) gas chromatography (GC) provides enhanced vapor separation capabilities in contrast to conventional one-dimensional GC and is useful for the analysis of highly complex chemical samples. We developed a microfabricated flow-restricted pneumatic modulator (FRPM) for portable comprehensive 2D micro-GC (µGC), which enables rapid 2D injection and separation without compromising the 1D separation speed and eluent peak profiles. 2D injection characteristics such as injection peak width and peak height were fully characterized by using flow-through micro-photoionization detectors (µPIDs) at the FRPM inlet and outlet. A 2D injection peak width of ~25 ms could be achieved with a 2D/1D flow rate ratio over 10. The FRPM was further integrated with a 0.5-m long 2D µcolumn on the same chip, and its performance was characterized. Finally, we developed an automated portable comprehensive 2D µGC consisting of a 10 m OV-1 1D µcolumn, an integrated FRPM with a built-in 0.5 m polyethylene glycol 2D µcolumn, and two µPIDs. Rapid separation of 40 volatile organic compounds in ~5 min was demonstrated. A hybrid 2D contour plot was constructed by using both 1D and 2D chromatograms obtained with the two µPIDs at the end of the 1D and 2D µcolumns, which was enabled by the presence of the flow resistor in the FRPM.

Lignin-assisted construction of sub-10 nm supramolecular self-assembly for photothermal immunotherapy and potentiating anti-PD-1 therapy against primary and distant breast tumors.

Photothermal therapy (PTT) has brought hope for cancer treatments, with hyperthermia-induced immunogenic cell death (ICD), which is a critical part of therapeutically induced antitumor immune responses. Limited immune stimulation response in PTT is the primary reason for incomplete tumor ablation, therefore demonstrating urgent requirements for ICD amplifier. Herein, a sub-10 nm supramolecular nanoassembly was formed by co-assembly of clinically approved aluminum adjuvant and commonly used indocyanine green (ICG) under the assistance of lignosulfonate (LS, a green and sustainable multifunctional lignin derivative) for localized photothermal-immunotherapy of breast cancer. The overall results revealed that LS-Al-ICG is capable of inducing amplified ICD, efficiently eliciting solid immune responses through dendritic cells (DCs) activation and cytotoxic T-cell responses initiation for tumor killing. Moreover, anti-PD-1 therapy blocked the PD-1 pathway and led to remarkable anti-tumor efficacy against laser-irradiated primary tumors and distant tumors by potentiating systemic tumor specific T cell immunity. The results of this study demonstrate a handy and extensible approach for engineering green natural lignin nanoparticles for cancer immunotherapy, which shows promise for delivering other therapeutics in biomedical applications.

Cooperative coordination-mediated multi-component self-assembly of "all-in-one" nanospike theranostic nano-platform for MRI-guided synergistic therapy against breast cancer.

Carrier-free multi-component self-assembled nano-systems have attracted widespread attention owing to their easy preparation, high drug-loading efficiency, and excellent therapeutic efficacy. Herein, MnAs-ICG nanospike was generated by self-assembly of indocyanine green (ICG), manganese ions (Mn2+), and arsenate (AsO4 3-) based on electrostatic and coordination interactions, effectively integrating the bimodal imaging ability of magnetic resonance imaging (MRI) and fluorescence (FL) imaging-guided synergistic therapy of photothermal/chemo/chemodynamic therapy within an "all-in-one" theranostic nano-platform. The as-prepared MnAs-ICG nanospike had a uniform size, well-defined nanospike morphology, and impressive loading capacities. The MnAs-ICG nanospike exhibited sensitive responsiveness to the acidic tumor microenvironment with morphological transformation and dimensional variability, enabling deep penetration into tumor tissue and on-demand release of functional therapeutic components. In vitro and in vivo results revealed that MnAs-ICG nanospike showed synergistic tumor-killing effect, prolonged blood circulation and increased tumor accumulation compared to their individual components, effectively resulting in synergistic therapy of photothermal/chemo/chemodynamic therapy with excellent anti-tumor effect. Taken together, this new strategy might hold great promise for rationally engineering multifunctional theranostic nano-platforms for breast cancer treatment.

Development and characterization of novelly grown fire-resistant fungal fibers.

This study conducted a comprehensive characterization and analyses on the fire-resistant behaviors of novel fungal fibers grown with substrate containing Silica (Si) source at multiple scales. At micro-scale, the results of SEM showed that silica affected the physiological activities of fungi, with the extent of effects depending upon its concentration. Fourier-transform infrared (FTIR) spectra displayed the existence of Si-O-C chemical bonds in fungal fibers grown with Si source, indicating that Si source becomes a part of the structure of fungal fibers. Thermogravimetric analysis (TGA) and Microscale combustion calorimetry (MCC) of fungal fibers exhibit an early thermal decomposition of non-combustible components, which will potentially help release the thermal stress and mitigation of spalling when used in concrete. Compared with polypropylene (PP) fibers, fungal fibers have a lower thermal degradation rate, a higher residual weight, a lower heat release peak temperature, and less total heat of combustion; all of these indicate improved thermal stability and fire resistance, and a lower rate of function loss in case of a fire. Additionally, the thermal stability and fire resistance of fungal fibers were improved with the increase of Si source concentration in the nutrition medium. For example, addition of 2% Si source in the feeding substrate leads to a 23.21% increase in residual weight in TGA, and a 23.66 W/g decrease in peak heat release rate as well as a 2.44 kJ/g reduction in total heat of combustion in MCC. At laboratory scale, compared with PP fibers, fungal fibers grown with 2% Si source have a higher residual weight of 40.40%, a higher ignition temperature of 200.50 °C, and a declined flame height of 11.64 mm in real fire scenarios. Furthermore, only in the fungal fibers grown with Si source, partial burning occurred. In post-fire conditions, the microstructure of residual char from fungal fibers grown with higher content of Si source became denser, which would lead to a reduction of the fuel vapor release and heat transfer. FTIR spectra of residual char demonstrated that fungal fibers grown with Si source formed more stable chemical bonds with higher heat of chemical bond formation, contributing to improved thermal stability and fire resistance. Therefore, compared with traditional fibers used for fiber reinforced concrete, incorporating the new natural grown fibers will potentially further improve the fire resistance of concrete and mitigate the concrete spalling.

Breath analysis for detection and trajectory monitoring of acute respiratory distress syndrome in swine.

Despite the enormous impact on human health, acute respiratory distress syndrome (ARDS) is poorly defined, and its timely diagnosis is difficult, as is tracking the course of the syndrome. The objective of this pilot study was to explore the utility of breath collection and analysis methodologies to detect ARDS through changes in the volatile organic compound (VOC) profiles present in breath. Five male Yorkshire mix swine were studied and ARDS was induced using both direct and indirect lung injury. An automated portable gas chromatography device developed in-house was used for point of care breath analysis and to monitor swine breath hourly, starting from initiation of the experiment until the development of ARDS, which was adjudicated based on the Berlin criteria at the breath sampling points and confirmed by lung biopsy at the end of the experiment. A total of 67 breath samples (chromatograms) were collected and analysed. Through machine learning, principal component analysis and linear discrimination analysis, seven VOC biomarkers were identified that distinguished ARDS. These represent seven of the nine biomarkers found in our breath analysis study of human ARDS, corroborating our findings. We also demonstrated that breath analysis detects changes 1-6 h earlier than the clinical adjudication based on the Berlin criteria. The findings provide proof of concept that breath analysis can be used to identify early changes associated with ARDS pathogenesis in swine. Its clinical application could provide intensive care clinicians with a noninvasive diagnostic tool for early detection and continuous monitoring of ARDS.

Phase shift approach for engineering desired radiation force: Acoustic pulling force example.

Phase shifts from scattering are used to analyze and engineer acoustic radiation forces. With the aid of phase shifts, analytical results for acoustic radiation forces can be simplified into compact and physically meaningful expressions, which can be used to develop a simplified procedure for the engineering of the radiation force. The desired radiation force can be fulfilled by a specific set of phase shifts up to a certain order, and then the required phase shifts can be fulfilled by engineering object and beam parameters. As an example, the phase shift approach is used to engineer the inner-to-outer radius ratio and the outer radius of a spherical shell to show how to use the phase shift method for the design of acoustic radiation forces. The example here is a force that is desired to pull particles against the propagation of a Bessel beam. A small paraxial parameter to pull a spherical shell is satisfied by in-phase scattering of monopole, dipole, quadrupole, octupole, and beyond. The example presented here is relatively simple yet reveals the advantages of the phase shift approach. The phase shift method can provide a simplified route for the design of acoustic tweezers using either traveling beams or standing waves.

High-Sensitivity Micro-Gas Chromatograph-Photoionization Detector for Trace Vapor Detection.

Rapid in situ detection and analysis of trace vapor concentrations at a sub-parts per billion to parts per trillion level remains a challenge for many applications such as indoor air-quality analysis and detection of explosives and narcotics. Micro-gas chromatography (µGC) together with a micro-photoionization detector (µPID) is a prominent method for portable analysis of complex vapor mixtures, but current µPID technology demonstrates poor detection performance compared to benchtop flame ionization detectors (FIDs). This work demonstrates the development of a significantly improved µPID with a sub-picogram detection limit (as low as ∼0.2 pg) comparable to or exceeding that of a benchtop FID, with a large linear dynamic range (>4 orders of magnitude) and robustness (high stability over 200 h of plasma activation). Based on this µPID, a complete µGC-PID system was built and tested on standard sample chromatograms in a laboratory setting to show the system's analytical capabilities and the detection limit down to sub-parts per trillion concentrations (as low as 0.14 ppt). Practical in-field chromatograms on breath and car exhaust were also generated to demonstrate applicability for in situ experimentation. This work shows that µGC-PID systems can be competitive with traditional GC-FID methods and thus opens a door to rapid trace vapor analysis in the field.

Lipid/PAA-coated mesoporous silica nanoparticles for dual-pH-responsive codelivery of arsenic trioxide/paclitaxel against breast cancer cells.

Nanomedicine has attracted increasing attention and emerged as a safer and more effective modality in cancer treatment than conventional chemotherapy. In particular, the distinction of tumor microenvironment and normal tissues is often used in stimulus-responsive drug delivery systems for controlled release of therapeutic agents at target sites. In this study, we developed mesoporous silica nanoparticles (MSNs) coated with polyacrylic acid (PAA), and pH-sensitive lipid (PSL) for synergistic delivery and dual-pH-responsive sequential release of arsenic trioxide (ATO) and paclitaxel (PTX) (PL-PMSN-PTX/ATO). Tumor-targeting peptide F56 was used to modify MSNs, which conferred a target-specific delivery to cancer and endothelial cells under neoangiogenesis. PAA- and PSL-coated nanoparticles were characterized by TGA, TEM, FT-IR, and DLS. The drug-loaded nanoparticles displayed a dual-pH-responsive (pHe = 6.5, pHendo = 5.0) and sequential drug release profile. PTX within PSL was preferentially released at pH = 6.5, whereas ATO was mainly released at pH = 5.0. Drug-free carriers showed low cytotoxicity toward MCF-7 cells, but ATO and PTX co-delivered nanoparticles displayed a significant synergistic effect against MCF-7 cells, showing greater cell-cycle arrest in treated cells and more activation of apoptosis-related proteins than free drugs. Furthermore, the extracellular release of PTX caused an expansion of the interstitial space, allowing deeper penetration of the nanoparticles into the tumor mass through a tumor priming effect. As a result, FPL-PMSN-PTX/ATO exhibited improved in vivo circulation time, tumor-targeted delivery, and overall therapeutic efficacy.

Real Time Breath Analysis Using Portable Gas Chromatography for Adult Asthma Phenotypes.

Asthma is heterogeneous but accessible biomarkers to distinguish relevant phenotypes remain lacking, particularly in non-Type 2 (T2)-high asthma. Moreover, common clinical characteristics in both T2-high and T2-low asthma (e.g., atopy, obesity, inhaled steroid use) may confound interpretation of putative biomarkers and of underlying biology. This study aimed to identify volatile organic compounds (VOCs) in exhaled breath that distinguish not only asthmatic and non-asthmatic subjects, but also atopic non-asthmatic controls and also by variables that reflect clinical differences among asthmatic adults. A total of 73 participants (30 asthma, eight atopic non-asthma, and 35 non-asthma/non-atopic subjects) were recruited for this pilot study. A total of 79 breath samples were analyzed in real-time using an automated portable gas chromatography (GC) device developed in-house. GC-mass spectrometry was also used to identify the VOCs in breath. Machine learning, linear discriminant analysis, and principal component analysis were used to identify the biomarkers. Our results show that the portable GC was able to complete breath analysis in 30 min. A set of nine biomarkers distinguished asthma and non-asthma/non-atopic subjects, while sets of two and of four biomarkers, respectively, further distinguished asthmatic from atopic controls, and between atopic and non-atopic controls. Additional unique biomarkers were identified that discriminate subjects by blood eosinophil levels, obese status, inhaled corticosteroid treatment, and also acute upper respiratory illnesses within asthmatic groups. Our work demonstrates that breath VOC profiling can be a clinically accessible tool for asthma diagnosis and phenotyping. A portable GC system is a viable option for rapid assessment in asthma.

Enhancing Hydrodeoxygenation of Bio-oil via Bimetallic Ni-V Catalysts Modified by Cross-Surface Migrated-Carbon from Biochar.

Aromatics from selective hydrodeoxygenation (HDO) of biomass-derived bio-oil are an ideal feedstock for replacing industrial fossil products. In this study, biochar-modified Hß/Ni-V catalysts were prepared and tested in the atmospheric HDO of guaiacol and bio-oil to produce aromatics. Compared with unmodified Hß/Ni-V, higher HDO activity was achieved in catalysts with all kinds of biochar modifications. Especially, the pine nut shell biochar (PB)-modified PB-Hß-8/Ni-V showed the highest selectivity to aromatics (69.17%), mainly including benzene and toluene. Besides, under the conditions of 380 °C and weight hourly space velocity (WHSV) of 0.5 h-1, the cleavage of CAr-OH (CAr means the carbon in the benzene ring) was promoted to form more aromatics. Moreover, great recyclability (58.77% aromatics for the reactivated run-3 test) and efficient HDO of bio-oil (44.9% aromatic yield) were also achieved. Based on the characterization results, the enhanced aromatic selectivity of PB-Hß-8/Ni-V was attributed to the synergetic effect between PB and Hß/Ni-V. In detail, a stable surface migrated-carbon layer was formed on Hß/Ni-V via the metal catalytic chemical vapor deposition (CVD) process of the pyrolysis PB volatiles. Simultaneously, a carbothermal reduction driven by the migrated-carbon took place to decorate the surface metals, obtaining more Ni0 and V3+ active sites. With this synergism, increased Ni0 sites promoted H2 adsorption and dissociation, which improved the hydrogenation activity. Furthermore, the higher affinity of the reactant and increased oxygen vacancies both contributed to enhancing the selective surface adsorption of oxygenous groups and the cleavage of the CAr-OH bond, thus improving the deoxygenation activity. Therefore, the HDO activity was improved to form more target aromatics over biochar-modified catalysts. This work highlighted a potential avenue to develop economic and environmental catalysts for the upgrading of bio-oil.

Genetic variants in MIR17HG affect the susceptibility and prognosis of glioma in a Chinese Han population.

BACKGROUND: lncRNA MIR17HG was upregulated in glioma, and participated in promoting proliferation, migration and invasion of glioma. However, the role of MIR17HG polymorphisms in the occurrence and prognosis of glioma is still unclear. METHODS: In the study, 592 glioma patients and 502 control subjects were recruited. Agena MassARRAY platform was used to detect the genotype of MIR17HG polymorphisms. Logistic regression analysis was used to evaluate the relationship between MIR17HG single nucleotide polymorphisms (SNPs) and glioma risk by odds ratio (OR) and 95% confidence intervals (CIs). Kaplan-Meier curves, Cox hazards models were performed for assessing the role of these SNPs in glioma prognosis by hazard ratios (HR) and 95% CIs. RESULTS: We found that rs7318578 (OR = 2.25, p = 3.18 × 10- 5) was significantly associated with glioma susceptibility in the overall participants. In the subgroup with age <  40 years, rs17735387 (OR = 1.53, p = 9.05 × 10- 3) and rs7336610 (OR = 1.35, p = 0.016) were related to the higher glioma susceptibility. More importantly, rs17735387 (HR = 0.82, log-rank p = 0.026) were associated with the longer survival of glioma patients. The GA genotype of rs17735387 had a better overall survival (HR = 0.75, log-rank p = 0.013) and progression free survival (HR = 0.73, log-rank p = 0.032) in patients with I-II glioma. We also found that rs72640334 was related to the poor prognosis (HR = 1.49, Log-rank p = 0.035) in female patients. In the subgroup of patients with age ≥ 40 years, rs17735387 was associated with a better prognosis (HR = 0.036, Log-rank p = 0.002). CONCLUSION: Our study firstly reported that MIR17HG rs7318578 was a risk factor for glioma susceptibility and rs17735387 was associated with the longer survival of glioma among Chinese Han population, which might help to enhance the understanding of MIR17HG gene in gliomagenesis. In subsequent studies, we will continue to collect samples and follow up to further validate our findings and further explore the function of these MIR17HG SNPs in glioma in a larger sample size.

Ethyl acetate extract of herpetospermum pedunculosum alleviates α-naphthylisothiocyanate-induced cholestasis by activating the farnesoid x receptor and suppressing oxidative stress and inflammation in rats.

BACKGROUND: Traditionally, seeds of Herpetospermum pedunculosum were used to treat liver disease or cholepathy. Up to date, their protecting effect against cholestasis was remain unclarified. PURPOSE: To investigate the efficacy, possible mechanisms, and active constituents of the ethyl acetate extract from the seeds of Herpetospermum pedunculosum (HPEAE), studies were carried out using cholestasis rat model induced by α-naphthylisothiocyanate (ANIT). METHODS: Male rats were intragastrically treated with HPEAE (100, 200 or 400 mg/kg) once a day for 7 days and were modeled with ANIT (60 mg/kg). The levels of serum indicators, bile flow, and histopathology were evaluated. Indices of oxidative stress and inflammatory mediators were detected using the enzyme-linked immunosorbent assay. Western blotting method was employed for analyzing the protein levels in the signal pathways of farnesoid X receptor (FXR), kelch ech associating protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) and nuclear factor κB (NF-κB). The chemical compositions of HPEAE was analyzed by HPLC, and partially chemical components of HPEAE were identified by comparisons of their retention times with the standards. The FXR agonistic activity of the identified compounds was evaluated in l-02 cells induced by guggulsterone using a high-content screening system. RESULTS: The cholestasis caused by ANIT can be significantly ameliorated by restoring the liver function indexes of alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyltransferase, total bilirubin, direct bilirubin and total bile acid, which are dose-dependent, as well as pathological liver injury and bile flow. Mechanical studies suggested that HPEAE can activate the expression of FXR and then up regulate its downstream proteins (multidrug resistance-associated protein 2, bile salt export pump and Na+/taurocholate cotransporting polypeptide). Moreover, the levels of the active oxygen index glutathione, superoxide dismutase, glutathione peroxidase, catalase and malondialdehyde were markedly restored by treatment with HPEAE. Western blotting further confirmed that HPEAE up regulated the expression of quinone oxidoreductase 1, heme oxygenase 1 and Keap1, lowered the expression of Nrf2 and reduced oxidative stress. HPEAE also up regulated P-glycoprotein 65, phosphorylated P-glycoprotein 65 and inhibitor of NF-κB kinase α expression, down regulated inhibitor of NF-κB (IκB), restored inflammatory mediator tumor necrosis factor-α, interleukin-1ß (IL-1ß), IL-6 and IL-10, and reduced inflammatory response. Fifteen compounds were identified (12 lignans and 3 coumarins). Among them, five lignans exhibited the significant FXR agonistic activity in vitro. CONCLUSION: HPEAE may alleviate the cholestasis and liver injury caused by ANIT in rats by activating FXR, as well as suppressing the Keap1/Nrf2 and NF-κB signaling pathways and lignans may be its main active components.